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Core–Shell Droplet-Based Angiogenic Patches for the Treatment of Ischemic Diseases: Ultrafast Processability, Physical Tunability, and Controlled Delivery of an Angiogenic Cocktail
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-10-09 , DOI: 10.1021/acsami.3c09062
Thi Van Anh Bui 1, 2 , Jin-Ju Kim 3, 4 , Xin Huang 1 , Aoyang Pu 1, 2 , Xin Li 1 , Seok Beom Hong 5 , Yeon-Jik Choi 6 , Hae-Won Kim 7, 8, 9 , Xi Yao 1 , Hun-Jun Park 3, 4 , Kiwon Ban 1, 2
Affiliation  

The patch-based delivery system has been a promising therapeutic approach for treating various vascular diseases. However, conventional methods face several challenges, including labor-intensive and time-consuming processes associated with patch fabrication or factor incorporation, inadequate physical properties, and uncontrolled release of factors. These limitations restrict the potential applications in clinical settings. To overcome these issues, we propose a novel core–shell-shaped droplet patch system called an angiogenic patch (AP). Our system offers several distinct advantages over conventional patches. It enables a rapid and straightforward fabrication process utilizing only two biodegradable ingredients [alginate and ε-poly(l-lysine)], ensuring minimal toxicity. Moreover, the AP exhibits excellent physical integrity to match and withstand physiological mechanics and allows for customizable patch dimensions tailored to individual patients’ pathological conditions. Notably, the AP enables facile loading of angiogenic cytokines during patch fabrication, allowing sustained release at a controlled rate through tunable network cross-linking. Subsequently, the AP, delivering a precisely formulated cocktail of angiogenic cytokines (VEGF, bFGF, EGF, and IGF), demonstrated significant effects on endothelial cell functions (migration and tubule formation) and survival under pathological conditions simulating ischemic injury. Likewise, in in vivo experiments using a mouse model of hindlimb ischemia, the AP encapsulating the angiogenic cocktail effectively restored blood flow following an ischemic insult, promoting muscle regeneration and preventing limb loss. With its simplicity and rapid processability, user-friendly applicability, physical tunability, and the ability to efficiently load and control the delivery of angiogenic factors, the AP holds great promise as a therapeutic means for treating patients with ischemic diseases.

中文翻译:

用于治疗缺血性疾病的基于核壳液滴的血管生成贴片:血管生成混合物的超快加工性、物理可调性和受控输送

基于贴片的输送系统已成为治疗各种血管疾病的一种有前途的治疗方法。然而,传统方法面临着一些挑战,包括与贴片制造或因子掺入相关的劳动密集型和耗时的过程、物理特性不足以及因子不受控制的释放。这些限制限制了其在临床环境中的潜在应用。为了克服这些问题,我们提出了一种新型的核壳形液滴贴片系统,称为血管生成贴片(AP)。与传统贴片相比,我们的系统具有几个明显的优势。它仅利用两种可生物降解成分[藻酸盐和ε-聚( l-赖氨酸)]实现快速、简单的制造过程,确保毒性最小。此外,AP 表现出出色的物理完整性,可以匹配和承受生理力学,并允许根据个别患者的病理状况定制贴片尺寸。值得注意的是,AP 能够在贴片制造过程中轻松加载血管生成细胞因子,从而通过可调节的网络交联以受控速率持续释放。随后,AP 提供了精确配制的血管生成细胞因子(VEGF、bFGF、EGF 和 IGF)混合物,在模拟缺血性损伤的病理条件下对内皮细胞功能(迁移和小管形成)和存活产生显着影响。同样,在使用后肢缺血小鼠模型的体内实验中,封装血管生成混合物的 AP 有效地恢复了缺血性损伤后的血流,促进肌肉再生并防止肢体丧失。凭借其简单性和快速加工性、用户友好的适用性、物理可调性以及有效加载和控制血管生成因子递送的能力,AP作为治疗缺血性疾病患者的治疗手段具有广阔的前景。
更新日期:2023-10-09
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